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Mosaicism of HTLV-1 5' LTR CpG methylation in the absence of malignancy.
Sibon, David; Zane, Linda; Idrissi, Manale El; Delfau-Larue, Marie-Hélène; Gessain, Antoine; Gout, Olivier; Mortreux, Franck; Wattel, Eric.
Afiliación
  • Sibon D; Université de Lyon 1, CNRS UMR5239, Oncovirologie et Biothérapies, Centre Léon Bérard, Lyon, France; Service d'Hématologie Adultes, Hôpital Universitaire Necker-Enfants Malades, AP-HP, Sorbonne Paris Cité, Paris, France.
Virus Res ; 178(2): 452-61, 2013 Dec 26.
Article en En | MEDLINE | ID: mdl-24036230
ABSTRACT
Viral expression varies widely between untransformed HTLV-1 positive clones derived from infected individuals without malignancy. Here we show that, in the absence of malignancy, 68% of HTLV-1 positive clones carry deleted (10%) or methylated (58%) 5' LTR. These changes were found to contribute to the fluctuation of viral expression between clones. 5' LTR deletions strongly impaired tax expression and thereby clonal expansion, telomere homeostasis, and genetic instability. The effects of CpG methylation on viral transcription were qualitatively and quantitatively different from those of LTR deletions and preserved the preleukemic features of HTLV-1(+)CD4(+) clones. 5' LTR methylation varied not only between clones but also between cells belonging to the same clones, between distinct integrated sequences within the same cells, and between CpG dyads along the 5' LTR. Such distributions suggest that a dynamic methylation spectrum might help sustain persistent infection.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Virus Linfotrópico T Tipo 1 Humano / Infecciones por HTLV-I / Metilación de ADN / Secuencias Repetidas Terminales Idioma: En Revista: Virus Res Asunto de la revista: VIROLOGIA Año: 2013 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Virus Linfotrópico T Tipo 1 Humano / Infecciones por HTLV-I / Metilación de ADN / Secuencias Repetidas Terminales Idioma: En Revista: Virus Res Asunto de la revista: VIROLOGIA Año: 2013 Tipo del documento: Article